Arthritic Bones May Be Due to Bugs in the Gut

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Scientists at the NYU School of Medicine have linked a species of intestinal bacteria known as Prevotella copri to the onset of rheumatoid arthritis (RA). The researchers, who collaborated with Harvard Medical School on a study entitled “Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis,” say this represents the first demonstration in humans that the chronic inflammatory joint disease may be mediated in part by specific intestinal bacteria.

Performing DNA analysis to compare gut bacteria from fecal samples of patients with rheumatoid arthritis and healthy individuals, the researchers found that P. copri was more abundant in patients newly diagnosed with rheumatoid arthritis than in healthy individuals or patients with chronic, treated rheumatoid arthritis.

“We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients,” write the investigators in eLife. “Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA.”

“Studies in rodent models have clearly shown that the intestinal microbiota contribute significantly to the causation of systemic autoimmune diseases,” adds Dan R. Littman, M.D., Ph.D., the Helen L. and Martin S. Kimmel Professor of Pathology and Microbiology and a Howard Hughes Medical Institute investigator. “At this stage, however, we cannot conclude that there is a causal link between the abundance of P. copri and the onset of rheumatoid arthritis. We are developing new tools that will hopefully allow us to ask if this is indeed the case.”

Why P. copri growth seems to take off in newly diagnosed patients with rheumatoid arthritis is also unclear, the researchers point out. Both environmental influences (e.g., diet) and genetic factors can shift bacterial populations within the gut, which may set off a systemic autoimmune attack. Adding to the mystery, P. copri extracted from stool samples of newly diagnosed patients appears genetically distinct from P. copri found in healthy individuals, the researchers found.

The researchers plan to validate their results in regions beyond New York, since gut flora can vary across geographical regions, and investigate whether the gut flora can be used as a biological marker to guide treatment. The ultimate goal is to develop novel treatments and diagnostics for RA.